Bayer Plc & Anor v NHS Darlington CCG & Ors

A policy encouraging off-label use of a cheaper medicine is lawful where realistic and lawful methods of implementation exist. Compounded medicine falls outside the marketing and manufacturing authorisation requirements only if the strict conditions identified by the CJEU are satisfied. Compounding must cause no inherent change to the medicinal substance and must occur under a system of prior individual prescriptions. It must also be undertaken in a dispensing pharmacy, or by a legally authorised person, solely for retail supply.

A policy need not prescribe every operational detail or prohibit every potentially unlawful method where implementation belongs to independent bodies capable of taking legal advice. Cost may properly influence prescribing where the available medicines have equivalent safety and efficacy and patients receive sufficient information.

The respondent clinical commissioning groups adopted a policy encouraging NHS trusts to offer Avastin as the preferred treatment for wet age-related macular degeneration. Avastin was substantially cheaper than the licensed alternatives, Lucentis and Eylea, but its ophthalmic use was off-label and ordinarily involved division into single-dose syringes.

The pharmaceutical companies sought judicial review, alleging that implementation would contravene the EU and domestic regimes governing the marketing, manufacture and distribution of medicines, undermine that regime and conflict with professional prescribing guidance. Whipple J dismissed the claim on 21 September 2018.

The central questions on appeal were whether the preparation and supply of compounded Avastin could satisfy the conditions derived from the CJEU's Apozyt jurisprudence, and whether the policy was unlawful because it left NHS trusts to choose how supplies would be obtained.

1. Appeal dismissed. The preparation and supply of compounded Avastin did not require marketing or manufacturing authorisation where the conditions of the Apozyt exemption were observed. NHS trusts could therefore lawfully use it off-label in accordance with the policy.

2. The marketing-authorisation limb required both an absence of modification to the medicinal product and compounding solely on the basis of individual prescriptions. Modification meant a change inherent in the compounding process to the physical, chemical or biological properties of the medicinal substance which might significantly affect quality, efficacy or safety. A risk of contamination caused by defective quality control did not itself constitute such modification.

3. The prescriptions had to exist before compounding began. Their function was to mark the boundary between regulated upstream manufacture and supply and the downstream clinical treatment of particular patients. The requirement did not prevent large-scale production or require a particular syringe to be allocated to a named patient.

4. For the manufacturing-authorisation limb, compounding had to be undertaken in a dispensing pharmacy, or by a person legally authorised to perform it, solely for retail supply. Preparation within an NHS hospital pharmacy, or supply from one NHS hospital pharmacy to another, could satisfy those requirements. Such inter-trust supply was covered by the pharmacist exemption in section 10(1) of the Medicines Act 1968 and did not require a wholesale dealer's licence.

5. The lawfulness of supply by a commercial compounder could not be determined on the evidence. That uncertainty did not invalidate the policy. The policy was silent about sourcing, and independent NHS trusts were responsible for selecting a lawful method. It neither sanctioned nor encouraged an unlawful route. Lawful preparation within, or supply from, an NHS hospital pharmacy was both realistic and within the policy's contemplation.

6. Systematic use of the CJEU exemption did not unlawfully undermine the EU regulatory scheme. Its scope depended on the downstream, retail character of the supply, not its scale. Nor did professional guidance prohibit choosing off-label Avastin on cost grounds where the medicines were considered equally safe and effective and patients retained an informed choice.

Underhill LJ delivered the leading judgment. Floyd LJ and Rose LJ agreed. Rose LJ emphasised that the policy did not purport to guide the independent trusts on implementation and that lawful, realistic modes remained available.

1. Court of Appeal (Civil Division): The appeal was dismissed and the decision that the policy was lawful was upheld: [2020] EWCA Civ 449.
2. High Court, Administrative Court: Whipple J dismissed the pharmaceutical companies' application for judicial review in a judgment handed down on 21 September 2018. No neutral citation is stated in the judgment.